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. 2022 Jan-Feb;36(1):198-205.
doi: 10.21873/invivo.12691.

Amino Acids May Have Protective Effects on Salivary Glands of 5-FU-administered Mice

Rieko Fujiwara  1 , Koji Harada  2 , Tarannum Ferdous  1 , Katsuaki Mishima  1
Affiliations

Amino Acids May Have Protective Effects on Salivary Glands of 5-FU-administered Mice

Rieko Fujiwara et al. In Vivo. 2022 Jan-Feb.

Abstract

Background/aim: This study aimed to identify the most useful components of Elental® in the treatment of 5-fluorouracil (FU)-induced mucositis and salivary gland atrophy in mice.

Materials and methods: Mice (except the control group) were intraperitoneally injected with 5-FU. The mice received saline (control group and 5-FU group), dextrin (Dextrin group), amino acids (17AA group), or Elental® (Elental® group).

Results: The volume and weight of salivary glands was higher in 17AA and Elental® groups compared to 5-FU group. The number of mucous glands was higher, whereas the number of damaged granular ductal epithelial cells was lower in the salivary glands of all groups except the 5-FU group. Salivation was also decreased in the 5-FU group compared to the other groups.

Conclusion: Amino acids could be the most effective components of Elental® for protecting mouse salivary glands from 5-FU-induced atrophic changes, and might be useful in the treatment of oral mucositis in cancer patients.

Keywords: 5-flurouracil; Salivary gland; amino acid; elemental diet; oral mucositis.

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Conflict of interest statement

The Authors declare no conflicts of interest in relation to this study. The Authors are fully responsible for the content of this paper.

Figures

Figure 1
Figure 1. Experimental schedule. All mice (except those in the Control group) received 5-FU (40 mg/kg/day) intraperitoneally for 4 days (from day 0 to day 3). The Control group and the 5-FU group mice received saline orally (0.8 ml/day), the Elental® group received Elental® (0.43 g/0.8 ml/day), the Dextrin group received (0.34 g/0.8 ml/day) and the17AA group mice received a mixture of 17 kinds of amino acids (0.07 g/0.8 ml/day) orally for 8 days (day 0 to day 7). The mice were sacrificed on day 8.
Figure 2
Figure 2. Effect of Elental® or Elental® components on mice body weight and morphology. (A) Photos of mice. Notable macroscopical changes were not observed among the groups. (B) Change of body weight. 5-FU, Elental® or Elental® component did not affect mouse body weight. No significant difference of body weight was observed among the groups. Bars, SD.
Figure 3
Figure 3. Effect of Elental® or Elental® components on salivary glands. (A) Photos of salivary glands. The size of salivary glands was the lowest in the 5-FU group. (B) Change of salivary glands volume. The volume of salivary glands was greater in the 17AA and Elental® groups than all the other groups. #p<0.01; compared to the 5-FU group (Mann-Whitney U-test). (C) Change of salivary glands weight. The weight of salivary glands was higher in all groups than that in the 5-FU group. The salivary gland weight of Elental® group was the heaviest; the 17AA group had the second heaviest salivary glands. Bars, SD. #p<0.01; compared to the 5-FU group (Mann-Whitney U-test).
Figure 4
Figure 4. Histological changes of salivary glands in mice. (A) HE staining. Mucous gland size of the 5-FU group was bigger than that of the other groups. The yellow arrows show the mucous gland area of salivary gland. (B) Change of mucous gland number. The number of mucous glands was higher in the Control, Dextrin, 17AA and Elental® groups than that in the 5-FU group, whereas the 17AA and Elental® groups showed the highest number. #p<0.01; compared to the 5-FU group (Mann-Whitney U-test). (C) Change of damaged granular ductal epithelial cell number. The number of damaged granular ductal epithelial cells was higher in the 5-FU group than in all groups, and was lowest in the Elental® and 17AA groups. The yellow arrows show the disappearance or atrophy of granular ductal epithelial cells after 5-FU treatment. Bars, SD. #p<0.01; compared to the 5-FU group (Mann-Whitney U-test).
Figure 5
Figure 5. Changes in saliva secretion. The salivary response to pilocarpine was reduced in the 5-FU group. In contrast, pilocarpineinduced salivations were increased in the 17AA and Elental® groups compared to Dextrin group at 15, and 30 min after pilocarpine stimulation. Bars, SD. #p<0.01; compared to the 5-FU group (MannWhitney U-test).
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